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Exposure to pesticides is one of the main drivers of global bee decline. However, the occurrence of pesticides in bee-attracting crops remains underexposed due to the lack of efficient on-site screening approaches for multi-analyte monitoring. Utilizing color-encoded superparamagnetic microspheres, we constructed a portable 8-plex indirect competitive microsphere-based immunoassay for the simultaneous determination of multiple bee-hazardous residues (Bee-Plex). Through a single measurement within 40 min, Bee-Plex exhibited high sensitivities with IC 50 values of 0.04, 0.08, 0.14, 0.15, 0.78, 0.86, 7.72, and 8.79 ng/mL for imidacloprid, parathion, fipronil, emamectin, carbofuran, chlorpyrifos, fenpropathrin and carbaryl, respectively. Moreover, the implementation of multiple broad-specific antibodies enables a wide-range screening profile for 30 pesticides and pesticide metabolites, detecting 6 neonicotinoids, 6 N-methyl carbamates 6 organophosphates, 5 avermectins, 5 pyrethroids and 2 phenylpyrazoles. The combination of Bee-Plex screening (93 % accuracy) and LC-MS/MS confirmatory analysis revealed contaminations of neonicotinoids (100 %) and avermectins (70 %) in roses, with occurrence frequencies of 79 %, 79 %, 21 %, 21 %, 7 %, and 7 % for imidacloprid, acetamiprid, clothianidin, thiacloprid, imidaclothiz, and nitenpyram, respectively. Above all, this study offers a powerful analytical tool for rapid screening of multiple bee-hazardous pesticides, offering new insights in the occurrence of multi-pesticide contamination in ornamental plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intravenous (IV) ketamine and FDA-approved intranasal (IN) esketamine are increasingly used for treatment-resistant depression (TRD). Preliminary studies have suggested a synergistic effect of ketamine and lamotrigine, although the data are inconclusive. Herein, we report the response to serial ketamine/esketamine treatment among patients with TRD with or without lamotrigine therapy. In this historical cohort study, we included adult patients with TRD who received serial IV racemic ketamine (0.5 mg/kg over 40-100 min) or IN esketamine (56/84 mg) treatments. A change in depressive symptoms was assessed using the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) scale. There were no significant differences in response or remission rates among the patients on or not on lamotrigine during the ketamine/esketamine treatments. For a percent change in the QIDS-SR from baseline, no interaction was found between the lamotrigine groups and treatment number ( p = 0.70), nor the overall effect of the group ( p = 0.38). There was a trend towards lower dissociation (based on the CADSS score) among current lamotrigine users, especially in patients who received IV ketamine. A major limitation is the limited number of patients taking lamotrigine (n = 13). This preliminary study provides insufficient evidence that continuing lamotrigine therapy attenuates the antidepressant effect of repeated ketamine/esketamine; however, there seems to be a signal toward attenuating dissociation with lamotrigine in patients receiving serial ketamine treatments. Further observational studies or randomized controlled trials are needed to replicate these findings.

Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function 1-8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory., (© 2023. The Author(s).)

Over the past 20 years, high-throughput genomic assays have fundamentally changed how transposable elements (TEs) are studied. While short-read DNA sequencing has been at the heart of these efforts, novel technologies that generate longer reads are driving a shift in the field. Long-read sequencing now permits locus-specific approaches to locate individual TE insertions and understand their epigenetic and transcriptional regulation, while still profiling TE activity genome-wide. Here we provide detailed guidelines to implement Oxford Nanopore Technologies (ONT) sequencing to identify polymorphic TE insertions and profile TE epigenetic landscapes. Using human long interspersed element-1 (LINE-1, L1) as an example, we explain the procedures involved, including final visualization, and potential bottlenecks and pitfalls. ONT sequencing will be, in our view, a workhorse technology for the foreseeable future in the TE field., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Sex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH., Methods: All consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients' characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed., Results: Three hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome., Conclusions: In the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management., (© 2022. The Author(s).)

Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19 + B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19 + B cells, CD4 + CXCR5 + follicular helper T cells, and CD8 + CXCR5 + follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression.

We evaluated construct validity, responsiveness, and utility of change indicators of the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety administered as computerized adaptive test (CAT). Specifically, the CATs were compared to the Brief Symptom Inventory (BSI) using pre- and re-test data of adult patients treated for common mental disorders ( N = 400; median pre-to-re-test interval = 215 days). Construct validity was evaluated with Pearson's correlations and Cohen's d s; responsiveness with Pearson's correlations and pre-post effect sizes ( ES ); utility of change indicators with kappa coefficients and percentages of (dis)agreement. The results showed that the PROMIS CATs measure similar constructs as matching BSI scales. Under the assumption of measuring similar constructs, the CAT and BSI Depression scales were similarly responsive. For the Anxiety scales, we found a higher responsiveness for CAT ( ES = 0.64) compared to the BSI ( ES = 0.50). Finally, both CATs categorized the change scores of more patients as changed compared to matching BSI scales, indicating that the PROMIS CATs may be more able to detect actual change than the BSI. Based on these findings, the PROMIS CATs may be considered a modest improvement over matching BSI scales as tools for reviewing treatment progress with patients. We discuss several additional differences between the PROMIS CATs and the BSI to help test users choose instruments. These differences include the adopted measurement theory (Item Response Theory vs. Classical Test Theory), the mode of administration (CAT vs. fixed items), and the area of application (universal vs. predominantly clinical). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: PROMIS offers computerized adaptive tests (CAT) of patient-reported outcomes, using a single set of US-based IRT item parameters across populations and language-versions. The use of country-specific item parameters has local appeal, but also disadvantages. We illustrate the effects of choosing US or country-specific item parameters on PROMIS CAT T-scores., Study Design and Setting: Simulations were performed on response data from Dutch chronic pain patients (n = 1110) who completed the PROMIS Pain Behavior item bank. We compared CAT T-scores obtained with (1) US parameters; (2) Dutch item parameters; (3) US item parameters for DIF-free items and Dutch item parameters (rescaled to the US metric) for DIF items; (4) Dutch item parameters for all items (rescaled to the US metric)., Results: Without anchoring to a common metric, CAT T-scores cannot be compared. When scores were rescaled to the US metric, mean differences in CAT T-scores based on US vs. Dutch item parameters were negligible. However, 0.9%-4.3% of the T-score differences were larger than 5 points (0.5 SD)., Conclusion: The choice of item parameters can be consequential for individual patient scores. We recommend more studies of translated CATs to examine if strategies that allow for country-specific item parameters should be further investigated., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

We investigated longitudinal measurement invariance in the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety using two clinical samples with mood and anxiety disorders ( n = 640 and n = 528, respectively). Factor analysis was used to evaluate whether the item banks were sufficiently unidimensional at two test-occasions and whether the measured constructs remained the same over time. The results indicated that the item banks were sufficiently unidimensional, but the thresholds and residual variances of the constructs changed over time. However, using tentative rules of thumb, these invariance violations did not substantially affect the endorsement of a specific response category of a specific item at a specific test-occasion. Furthermore, the impact on the mean latent change scores of the item banks remained below the proposed cutoff value for substantial bias. These findings suggest that the invariance violations lacked practical significance for test-users, meaning that the item banks provide sufficiently invariant latent factor scores for use in clinical practice.

Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu (SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient-reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch-Flemish PROMIS pain interference (PROMIS-PI) and the PROMIS pain behavior (PROMIS-PB) item banks in patients with RA., Methods: A total of 2,029 patients with RA completed the full PROMIS-PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS-PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross-cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects., Results: The PROMIS-PI and PROMIS-PB banks were sufficiently unidimensional (Omega-hierarchical [Omega-H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3-1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross-cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively)., Conclusion: Both PROMIS-PI and PROMIS-PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice., (© 2019, American College of Rheumatology.)

In psychological assessment of children, it is pivotal to establish from what age on self-reports can complement or replace informant reports. We introduce a psychometric approach to estimate the minimum age for a child to produce self-report data that is of similar quality as informant data. The approach makes use of statistical validity indicators such as person-fit and long-string indices, and can be readily applied to data commonly collected in psychometric studies of child measures. We evaluate and illustrate the approach, using self-report and informant-report data of the PedsQL, a pediatric health-related quality of life measure, from 651 child-mother pairs. To evaluate the approach, we tested various hypotheses about the validity of the self-report data, using the G n p person-fit index as the validity indicator and the mother informant-data as a benchmark for validity. Results showed that G n p discriminated between self-reports of younger and older children, between self-reports of children that completed the PedsQL alone or with a parent, and between self-reports and informant reports. We conclude that the validity-index approach has good potential for future applications. Future research should further evaluate the approach for different types of questionnaires (e.g., personality inventories) and using different validity indices (e.g., response-bias indices).

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high-throughput screen within the European Lead Factory program. Structure-guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)-3-(4-carbamimidoylphenyl)-N-((S)-1-(naphthalen-1-yl)propyl)-2-oxooxazolidine-5-carboxamide) and 34 ((5R)-3-(6-carbamimidoylpyridin-3-yl)-N-((1S)-1-(naphthalen-1-yl)propyl)-2-oxooxazolidine-5-carboxamide) have single-digit nanomolar potency against KLK6, with over 25-fold and 100-fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32, effectively reduces KLK6-dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo., (©2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We used the Dutch-Flemish version of the USA PROMIS adult V1.0 item bank for Anxiety as input for developing a computerized adaptive test (CAT) to measure the entire latent anxiety continuum. First, psychometric analysis of a combined clinical and general population sample ( N = 2,010) showed that the 29-item bank has psychometric properties that are required for a CAT administration. Second, a post hoc CAT simulation showed efficient and highly precise measurement, with an average number of 8.64 items for the clinical sample, and 9.48 items for the general population sample. Furthermore, the accuracy of our CAT version was highly similar to that of the full item bank administration, both in final score estimates and in distinguishing clinical subjects from persons without a mental health disorder. We discuss the future directions and limitations of CAT development with the Dutch-Flemish version of the PROMIS Anxiety item bank.

Background: In the clinical field, the use of questionnaires is ubiquitous, and many different methods for constructing them are available. The reason for using a specific method is usually lacking, and a generally accepted classification of methods is not yet available. To guide test developers and users, this article presents a taxonomy for methods of questionnaire design which links the methods to the goal of a test., Methods: The taxonomy assumes that construction methods are directed towards psychometric aspects. Four stages of test construction are distinguished to describe methods: concept analysis, item production, scale construction, and evaluation; the scale construction stage is used for identifying methods. It distinguishes six different methods: the rational method utilizes expert judgments to ensure face validity. The prototypical method uses prototypicality judgments to ensure process validity. In the internal method, item sets are selected that optimize homogeneity. The external method optimizes criterion validity by selecting items that best predict an external criterion. Under the construct method theoretical considerations are used to optimize construct validity. The facet method is aimed at optimizing content validity through a complete representation of the concept domain., Conclusion: The taxonomy is comprehensive, constitutes a useful tool for describing procedures used in questionnaire design, and allows for setting up a test construction plan in which the priorities among psychometric aspects are made explicit.

Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

Background: Two important goals when using questionnaires are (a) measurement: the questionnaire is constructed to assign numerical values that accurately represent the test taker's attribute, and (b) prediction: the questionnaire is constructed to give an accurate forecast of an external criterion. Construction methods aimed at measurement prescribe that items should be reliable. In practice, this leads to questionnaires with high inter-item correlations. By contrast, construction methods aimed at prediction typically prescribe that items have a high correlation with the criterion and low inter-item correlations. The latter approach has often been said to produce a paradox concerning the relation between reliability and validity [1-3], because it is often assumed that good measurement is a prerequisite of good prediction., Objective: To answer four questions: (1) Why are measurement-based methods suboptimal for questionnaires that are used for prediction? (2) How should one construct a questionnaire that is used for prediction? (3) Do questionnaire-construction methods that optimize measurement and prediction lead to the selection of different items in the questionnaire? (4) Is it possible to construct a questionnaire that can be used for both measurement and prediction?, Illustrative Example: An empirical data set consisting of scores of 242 respondents on questionnaire items measuring mental health is used to select items by means of two methods: a method that optimizes the predictive value of the scale (i.e., forecast a clinical diagnosis), and a method that optimizes the reliability of the scale. We show that for the two scales different sets of items are selected and that a scale constructed to meet the one goal does not show optimal performance with reference to the other goal., Discussion: The answers are as follows: (1) Because measurement-based methods tend to maximize inter-item correlations by which predictive validity reduces. (2) Through selecting items that correlate highly with the criterion and lowly with the remaining items. (3) Yes, these methods may lead to different item selections. (4) For a single questionnaire: Yes, but it is problematic because reliability cannot be estimated accurately. For a test battery: Yes, but it is very costly. Implications for the construction of patient-reported outcome questionnaires are discussed.

Pseudomonas baetica strain a390T is the type strain of this recently described species and here we present its high-contiguity draft genome. To celebrate the 16th International Conference on Pseudomonas, the genome of P. baetica strain a390T was sequenced using a unique combination of Ion Torrent semiconductor and Oxford Nanopore methods as part of a collaborative community-led project. The use of high-quality Ion Torrent sequences with long Nanopore reads gave rapid, high-contiguity and -quality, 16-contig genome sequence. Whole genome phylogenetic analysis places P. baetica within the P. koreensis clade of the P. fluorescens group. Comparison of the main genomic features of P. baetica with a variety of other Pseudomonas spp. suggests that it is a highly adaptable organism, typical of the genus. This strain was originally isolated from the liver of a diseased wedge sole fish, and genotypic and phenotypic analyses show that it is tolerant to osmotic stress and to oxytetracycline.

Purpose: Multidimensional item response theory and computerized adaptive testing (CAT) are increasingly used in mental health, quality of life (QoL), and patient-reported outcome measurement. Although multidimensional assessment techniques hold promises, they are more challenging in their application than unidimensional ones. The authors comment on minimal standards when developing multidimensional CATs., Methods: Prompted by pioneering papers published in QLR, the authors reflect on existing guidance and discussions from different psychometric communities, including guidelines developed for unidimensional CATs in the PROMIS project., Results: The commentary focuses on two key topics: (1) the design, evaluation, and calibration of multidimensional item banks and (2) how to study the efficiency and precision of a multidimensional item bank. The authors suggest that the development of a carefully designed and calibrated item bank encompasses a construction phase and a psychometric phase. With respect to efficiency and precision, item banks should be large enough to provide adequate precision over the full range of the latent constructs. Therefore CAT performance should be studied as a function of the latent constructs and with reference to relevant benchmarks. Solutions are also suggested for simulation studies using real data, which often result in too optimistic evaluations of an item bank's efficiency and precision., Discussion: Multidimensional CAT applications are promising but complex statistical assessment tools which necessitate detailed theoretical frameworks and methodological scrutiny when testing their appropriateness for practical applications. The authors advise researchers to evaluate item banks with a broad set of methods, describe their choices in detail, and substantiate their approach for validation.

The countdown method is a well-known approach to reducing the average length of screening instruments that are presented by computer. In the countdown method, testing is terminated once the result of the screener ("positive" or "negative") has been unambiguously determined from prior answers. Previous research has examined whether presenting dichotomously scored items in order from "least to most frequently endorsed" or "most to least frequently endorsed" is more efficient when the countdown method is used. The current study describes the Mean Score procedure, an extension of the above item ordering procedures to polytomously scored items, and evaluates its efficiency relative to the distribution of other possible item orderings in 2 real-data simulations. Both simulations involve item responses to the Posttraumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5). In the first simulation, items were scored polytomously, and a single cutoff point was used to determine the screening result. In the second simulation, items were converted to dichotomous scores, as well as categorized into 4 clusters; a positive result for the entire assessment was obtained if and only if a positive result was obtained for each cluster. The latter simulation also investigated the effect of reordering the clusters themselves on the efficiency of the countdown method. Results indicated that the Mean Score procedure does not necessarily produce the optimal ordering, but tends to assemble an efficient item ordering relative to the distribution of possible orderings. In the second simulation, reordering the clusters themselves affected efficiency. Future research directions are suggested. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Background: The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item assessment designed to assist in the prediction of aberrant drug-related behavior (ADB) among patients with chronic pain. Recent work has created shorter versions of the SOAPP-R, including a static 12-item short form and two computer-based methods (curtailment and stochastic curtailment) that monitor assessments in progress. The purpose of this study was to cross-validate these shorter versions in two new populations., Methods: This retrospective study used data from patients recruited from a hospital-based pain center (n=84) and pain patients followed and treated at primary care centers (n=110). Subjects had been administered the SOAPP-R and assessed for ADB. In real-data simulation, the sensitivity, specificity, and area under the curve (AUC) of each form were calculated, as was the mean test length using curtailment and stochastic curtailment., Results: Curtailment reduced the number of items administered by 30% to 34% while maintaining sensitivity and specificity identical to those of the full-length SOAPP-R. Stochastic curtailment reduced the number of items administered by 45% to 63% while maintaining sensitivity and specificity within 0.03 of those of the full-length SOAPP-R. The AUC of the 12-item form was equal to that of the 24-item form in both populations., Conclusions: Curtailment, stochastic curtailment, and the 12-item short form have potential to enhance the efficiency of the SOAPP-R., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to assess the psychometric properties of the Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank in Dutch patients with chronic pain., Study Design and Setting: A bank of 121 items was administered to 1,247 Dutch patients with chronic pain. Unidimensionality was assessed by fitting a one-factor confirmatory factor analysis and evaluating resulting fit statistics. Items were calibrated with the graded response model and its fit was evaluated. Cross-cultural validity was assessed by testing items for differential item functioning (DIF) based on language (Dutch vs. English). Construct validity was evaluated by calculation correlations between scores on the Dutch-Flemish PROMIS Physical Function measure and scores on generic and disease-specific measures., Results: Results supported the Dutch-Flemish PROMIS Physical Function item bank's unidimensionality (Comparative Fit Index = 0.976, Tucker Lewis Index = 0.976) and model fit. Item thresholds targeted a wide range of physical function construct (threshold-parameters range: -4.2 to 5.6). Cross-cultural validity was good as four items only showed DIF for language and their impact on item scores was minimal. Physical Function scores were strongly associated with scores on all other measures (all correlations ≤ -0.60 as expected)., Conclusion: The Dutch-Flemish PROMIS Physical Function item bank exhibited good psychometric properties. Development of a computer adaptive test based on the large bank is warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item questionnaire designed to assess risk of aberrant medication-related behaviors in chronic pain patients. The introduction of short forms of the SOAPP-R may save time and increase utilization by practitioners., Objective: To develop and evaluate candidate SOAPP-R short forms., Design: Retrospective study., Setting: Pain centers., Subjects: Four hundred and twenty-eight patients with chronic noncancer pain., Methods: Subjects had previously been administered the full-length version of the SOAPP-R and been categorized as positive or negative for aberrant medication-related behaviors via the Aberrant Drug Behavior Index (ADBI). Short forms of the SOAPP-R were developed using lasso logistic regression. Sensitivity, specificity, and area under the curve (AUC) of all forms were calculated with respect to the ADBI using the complete data set, training-test analysis, and 10-fold cross-validation. The coefficient alpha of each form was also calculated. An external set of 12 pain practitioners reviewed the forms for content., Results: In the complete data set analysis, a form of 12 items exhibited sensitivity, specificity, and AUC greater than or equal to those of the full-length SOAPP-R (which were 0.74, 0.67, and 0.76, respectively). The short form had a coefficient alpha of 0.76. In the training-test analysis and 10-fold cross-validation, it exhibited an AUC value within 0.01 of that of the full-length SOAPP-R. The majority of external practitioners reported a preference for this short form., Conclusions: The 12-item version of the SOAPP-R has potential as a short risk screener and should be tested prospectively., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: To investigate the potential of customized computer-based testing procedures to reduce the mean test length of the Posttraumatic Stress Checklist for DSM-5 (PCL-5)., Method: A retrospective analysis was conducted using responses from 942 adults who had completed the full-length (20-item) PCL-5 in the aftermath of Hurricane Sandy. The abilities of 2 testing procedures, curtailment and stochastic curtailment, to lessen the instrument's mean test length while maintaining the same result as the full-length PCL-5 ("positive" or "negative") were evaluated in a post hoc simulation. Curtailment and stochastic curtailment track a respondent's answers as she takes the instrument and stop the test if future items are unable or unlikely to change the result. The performance of each procedure was recorded under 2 scoring methods: a total-score-based method and a cluster-based method. Each procedure's sensitivity, specificity, and overall agreement with the full-length PCL-5 were computed., Results: Curtailment reduced the mean test length by 40% under the total-score-based method, and by more than 70% under the cluster-based method, while exhibiting 100% sensitivity, specificity, and overall agreement with the full-length PCL-5. Stochastic curtailment reduced the mean test length by up to 88% under the total-score-based method, and up to 84% under the cluster-based method, while always exhibiting at least 92% sensitivity and 99.8% overall agreement, as well as 100% specificity, for the full-length PCL-5., Conclusions: Curtailment and stochastic curtailment have potential to enhance the efficiency of the PCL-5 when this assessment is administered by computer. The 2 procedures should be evaluated in future prospective studies. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

We developed a Dutch-Flemish version of the patient-reported outcomes measurement information system (PROMIS) adult V1.0 item bank for depression as input for computerized adaptive testing (CAT). As item bank, we used the Dutch-Flemish translation of the original PROMIS item bank (28 items) and additionally translated 28 U.S. depression items that failed to make the final U.S. item bank. Through psychometric analysis of a combined clinical and general population sample ( N = 2,010), 8 added items were removed. With the final item bank, we performed several CAT simulations to assess the efficiency of the extended (48 items) and the original item bank (28 items), using various stopping rules. Both item banks resulted in highly efficient and precise measurement of depression and showed high similarity between the CAT simulation scores and the full item bank scores. We discuss the implications of using each item bank and stopping rule for further CAT development.

Background: Respondents' scores to the Screener and Opioid Assessment for Patients with Pain - revised (SOAPP-R) have been shown to be predictive of aberrant drug-related behavior (ADB). However, research is lacking on whether an individual's completion time (the amount of time that he/she takes to finish the screener) has utility in predicting ADB, despite the fact that response speed has been useful in predicting behavior in other fields. The purpose of this study was to evaluate the degree to which SOAPP-R completion time is predictive of ADB., Materials and Methods: This retrospective study analyzed completion-time data from 82 adult emergency department patients who completed the SOAPP-R on a tablet computer. The utility of SOAPP-R completion times in predicting ADB was assessed via logistic regression and the area under the curve (AUC) statistic. An external measure of ADB using Prescription Drug Monitoring Program data defined ADB to have occurred in individuals with at least four opioid prescriptions and at least four prescribers in 12 months., Results: Although there was a slight trend for individuals with greater completion times to have greater odds of ADB (odds ratio 1.004 in simple logistic regression), the association between SOAPP-R completion time and ADB was not statistically significant in either simple logistic regression ( P =0.307) or multiple logistic regression adjusting for SOAPP-R score ( P =0.419). AUC values for the prediction of ADB using completion time alone, SOAPP-R score alone, and both completion time and SOAPP-R score were 0.63, 0.64, and 0.65, respectively., Conclusion: There was no significant evidence that SOAPP-R completion times were predictive of ADB among emergency department patients. However, the AUC value for completion times was only slightly less than that for SOAPP-R total scores., Competing Interests: DisclosureSFB is an employee of Inflexxion Inc. Inflexxion holds the copyright for the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP®-R). The other authors report no conflicts of interest in this work.

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Background: The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire measuring distress, depression, anxiety and somatization with separate scales. The 4DSQ has extensively been validated in clinical samples, especially from primary care settings. Information about measurement properties and normative data in the general population was lacking. In a Dutch general population sample we examined the 4DSQ scales' structure, the scales' reliability and measurement invariance with respect to gender, age and education, the scales' score distributions across demographic categories, and normative data., Methods: 4DSQ data were collected in a representative Dutch Internet panel. Confirmatory factor analysis was used to examine the scales' structure. Reliability was examined by Cronbach's alpha, and coefficients omega-total and omega-hierarchical. Differential item functioning (DIF) analysis was used to evaluate measurement invariance across gender, age and education., Results: The total response rate was 82.4 % (n = 5273/6399). The depression scale proved to be unidimensional. The other scales were best represented as bifactor models consisting of a large general factor and one or more smaller specific factors. The general factors accounted for more than 95 % of the reliable variance of the scales. Reliability was high (≥0.85) by all estimates. The distress-, depression- and anxiety scales were invariant across gender, age and education. The somatization scale demonstrated some lack of measurement invariance as a result of decreased thresholds for some of the items in young people (16-24 years) and increased thresholds in elderly people (65+ years). The somatization scale was invariant regarding gender and education. The 4DSQ scores varied significantly across demographic categories, but the explained variance was small (<6 %). Normative data were generated for gender and age categories. Approximately 17 % of the participants scored above average on de distress scale, whereas 12 % scored above average on de somatization scale. Percentages of people scoring high enough on depression or anxiety as to suspect the presence of depressive or anxiety disorder were 4.1 and 2.5 respectively., Conclusions: Evidence supports reliability and measurement invariance of the 4DSQ in the general Dutch population. The normative data provided in this study can be used to compare a subject's 4DSQ scores with a general population reference group.

In a post hoc simulation study (N = 3,597 psychiatric outpatients), we investigated whether the efficiency of the 90-item Mood and Anxiety Symptom Questionnaire (MASQ) could be improved for assessing clinical subjects with computerized adaptive testing (CAT). A CAT simulation was performed on each of the 3 MASQ subscales (Positive Affect, Negative Affect, and Somatic Anxiety). With the CAT simulation's stopping rule set at a high level of measurement precision, the results showed that patients' test administration can be shortened substantially; the mean decrease in items used for the subscales ranged from 56% up to 74%. Furthermore, the predictive utility of the CAT simulations was sufficient for all MASQ scales. The findings reveal that developing a MASQ CAT for clinical subjects is useful as it leads to more efficient measurement without compromising the reliability of the test outcomes. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Purpose: To increase the precision of estimated item parameters of item response theory models for patient-reported outcomes, general population samples are often enriched with samples of clinical respondents. Calibration studies provide little information on how this sampling scheme is incorporated into model estimation. In a small simulation study the impact of ignoring the oversampling of clinical respondents on item and person parameters is illustrated., Method: Simulations were performed using two scenarios. Under the first it was assumed that regular and clinical respondents form two distinct distributions; under the second it was assumed that they form a single distribution. A synthetic item bank with quasi-trait characteristics was created, and item scores were generated from this bank for samples with varying percentages of clinical respondents. Proper (using a multi-group model, and sample weights, respectively, for Scenarios 1 and 2) and improper (ignoring oversampling) approaches for dealing with the clinical sample were contrasted using correlations and differences between true and estimated parameters., Results: Under the first scenario, ignoring the sampling scheme resulted in overestimation of both item and person parameters with bias decreasing with higher percentages of clinical respondents. Under the second, location and person parameters were underestimated with bias increasing in size with increasing percentage of clinical respondents. Under both scenarios, the standard error of the latent trait estimate was generally underestimated., Conclusion: Ignoring the addition of extra clinical respondents leads to bias in item and person parameters, which may lead to biased norms and unreliable CAT scores. An appeal is made for researchers to provide more information on how clinical samples are incorporated in model estimation.

Purpose: We reevaluated the psychometric properties of the Amsterdam Inventory for Auditory Disability and Handicap (AIADH; Kramer, Kapteyn, Festen, & Tobi, 1995) using item response theory. Item response theory describes item functioning along an ability continuum., Method: Cross-sectional data from 2,352 adults with and without hearing impairment, ages 18-70 years, were analyzed. They completed the AIADH in the web-based prospective cohort study "Netherlands Longitudinal Study on Hearing." A graded response model was fitted to the AIADH data. Category response curves, item information curves, and the standard error as a function of self-reported hearing ability were plotted., Results: The graded response model showed a good fit. Item information curves were most reliable for adults who reported having hearing disability and less reliable for adults with normal hearing. The standard error plot showed that self-reported hearing ability is most reliably measured for adults reporting mild up to moderate hearing disability., Conclusions: This is one of the few item response theory studies on audiological self-reports. All AIADH items could be hierarchically placed on the self-reported hearing ability continuum, meaning they measure the same construct. This provides a promising basis for developing a clinically useful computerized adaptive test, where item selection adapts to the hearing ability of individuals, resulting in efficient assessment of hearing disability.

Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a more complete human cell model suitable for screening of drug-related interactions and nephrotoxicity. In addition to endogenously expressed renal organic cation transporters and efflux transporters, conditionally immortalized proximal tubule epithelial cells (ciPTEC) were completed by transduction of cells with the organic anion transporter (OAT) 1 or OAT3. Fluorescence-activated cell sorting upon exposure to the OAT substrate fluorescein successfully enriched transduced cells. A panel of organic anions was screened for drug-interactions in ciPTEC-OAT1 and ciPTEC-OAT3. The cytotoxic response to the drug-interactions with antivirals was further examined by cell viability assays. Upon subcloning, concentration-dependent fluorescein uptake was found with a higher affinity for ciPTEC-OAT1 (Km = 0.8 ± 0.1 μM) than ciPTEC-OAT3 (Km = 3.7 ± 0.5 μM). Co-exposure to known OAT1 and/or OAT3 substrates (viz. para-aminohippurate, estrone sulfate, probenecid, furosemide, diclofenac, and cimetidine) in cultures spanning 29 passage numbers revealed relevant inhibitory potencies, confirming the robustness of our model for drug-drug interactions studies. Functional OAT1 was directly responsible for cytotoxicity of adefovir, cidofovir, and tenofovir, while a drug interaction with zidovudine was not associated with decreased cell viability. Our data demonstrate that human-derived ciPTEC-OAT1 and ciPTEC-OAT3 are promising platforms for highly predictive drug screening during early phases of drug development.